Chemotherapeutic agents are known suppressors of red cell production by the bone marrow, and over 60% of patients treated with chemotherapy develop anemia resulting in decreased functional capacity and quality of life. In contrast to other common side effects experienced by patients undergoing treatment for cancer, chemotherapy-induced anemia (CIA) is often a “silent” side effect with insidious symptoms. CIA can be one of the most common underlying etiologies of the fatigue in cancer patients. Most chemotherapeutic agents also cause stomach upset, resulting in nausea and vomiting, which can severely reduce appetite and produce substantial weight loss in the patient. CIA is also associated with cognitive dysfunction, dyspnea, and depression. As a result of this reduced quality of life, some patients choose to discontinue or delay chemotherapeutic treatment, increasing the potential for suboptimal outcomes. Also, CIA can adversely affect long-term outcomes in some patients, as the anemic environment may limit the effectiveness of some chemotherapy agents.
The incidence and severity of CIA depend on a variety of factors, including the type, schedule, and intensity of therapy administered, or whether the patient has received prior myelosuppressive chemotherapy, radiation therapy, or both. Approximately 1.3 million cancer patients undergo chemotherapy every year in the United States, and approximately 67 percent become anemic. Similarly, approximately 63 percent of European chemotherapy patients develop anemia as a result of their treatment.
Although chemotherapy-induced anemia is one of the most common side effects of chemotherapy, it is often not recognized and is frequently under-treated. Treatments can include red blood cell transfusions, which may result in clinical or subclinical adverse effects in the recipients. Several clinical trials have demonstrated that treatment with erythropoeitic agents can reduce the need for blood transfusions and their associated complications in patients undergoing chemotherapy. Daily subcutaneous administration of recombinant human EPO administration at a dose of 5000 IU increases hemoglobin levels and reduces transfusion requirements in chemotherapy-induced anemia, especially during platinum-based chemotherapy. (Oberhoff et al. (1998) Ann Oncol 9:255-260.) However, clinical trials have suggested that a measurable increase in thrombotic complications occurs in chemotherapy-induced anemia patients treated with recombinant human EPO (rhEPO). (Wun et al. (2003) Cancer 98:1514-1520.) The overall impact on thrombosis risk has been confirmed in an independent meta-analysis of rhEPO data. (Bohlius et al. (2005) J Natl Cancer Inst 97(7):489-98.) Furthermore, it is estimated that 30% to 50% of patients undergoing chemotherapy and receiving recombinant human EPO treatment are hyporesponsive or refractory to the recombinant EPO therapy. (J. Glaspy (2005) Expert Opin. Emerging Drugs 10:553-567.) Such patients may then have to undergo treatment with blood transfusions, which is associated with certain risks, including transfusion-transmitted infection, incorrect blood transfusion, acute or delayed transfusion reaction, post-transfusion purpura, transfusion-associated graft-verses-host disease, etc. Thus, a need remains for effective treatments for chemotherapy-induced anemia. In particular, there is a need for effective treatments for chemotherapy-induced anemia in subjects refractory to EPO therapy.